Nerve growth factor (NGF) is a hormone-like protein that is important in the development of the nervous system, i.e., sympathetic and sensory ganglia, and in the maintenance of neurones in vivo and in vitro. This project is aimed at utilizing the powerful new approach with monoclonal antibodies to investigate the structural and functional interactions betweem nerve growth factor and its cellular receptor. Monoclonal antibodies have been obtained from hybridomas in our laboratory with specificity directed toward single antigenic determinants on mouse submaxillary and human placental beta NGF. These monoclonal antibodies will be used to differentiate binding of NGF to plasma membrane receptors and nuclear receptors of neurones from sympathetic and dorsal root ganglia and pheochromocytoma (PC 12) cells. The requirements of the active site of nerve growth factor will be examined by the ability of monoclonal antibodies directed toward the active site to combine with proteolytically cleaved fragments or chemically modified beta NGF. Monoclonal antibodies will also be developed that are directed toward the cellular receptor by immunization with partially purified receptors and selection of hybrid clones that produce the desired antibody. These anti-receptor (NGF) monoclonal antibodies will ascertain whether the various receptors are structurally related and whether neurons maintenance can be mimicked by receptor-antibody interaction on the cell surface. An examination of the structural requirements for immunosympathectomy by monoclonal antibodies against NGF (and its receptor will be made and correlated with molecular structure. New monoclonal-immunoassays will be used to examine levels of NGF and its receptor in mouse tissues, during development, and in human tumors. These aspects of the mechanism of action of hormone will allow a correlation with the developmental neurobiology and abnormal growth in which NGF may be involved. The function of NGF is relevant to neuronal differentiation and survival, neurological disorders, cell transformation, and tumorigenesis.